This proposal seeks to discover the intercellular signaling and specific neural circuit substrates of the loss and recovery of binocular responses in the visual cortex during the critical period of susceptibility to the effects of monocular visual deprivation. It also seeks to understand the differences between the high degree neural plasticity at the height of the critical period and reduced plasticity in the adult visual cortex. The methods to be used are efficient means of measuring visual responses and neural circuits longitudinally in individual mice, including transcranial intrinsic signal optical imaging, extracellular microelectrode recording, 2-photon laser scanning microscopy for longitudinal anatomical studies in vivo, and 2-photon laser scanning of multiple neurons bulk-filled with calcium indicators. The time course of visual cortical plasticity in response to monocular visual deprivation and recovery at the peak of the critical period consists of distinct temporal phases. Our preliminary results show these phases to be distinct in the molecular signals that operate in each phase, so that mice mutant in specific signaling pathways are deficient in only one of the three phases. We will determine in which cells of the upper cortical layers these mechanisms influence plasticity, and how these signaling pathways and neural plasticity in response to them change in adulthood.